Molecular diagnostic analyses are used for determining, for example, viral loads of HI viruses, hepatitis C and hepatitis B viruses. In a central laboratory, such analyses are nowadays often carried out on liquid-handling robotic systems. The reaction vessels used are microtiter plates, in particular 96-well plates having, for example, 8 rows of 12 wells. These wells are arranged at standardized intervals of about 0.9 cm from one another. Sample material and reagents are pipetted into predetermined wells of the titer plates by the liquid-handling robot in a freely programmable manner by means of pipet tips made of plastic or washable, reusable tips. Also, some processing steps, such as incubation at a certain temperature, mixing processes, or, for example, magnetic separation processes, are carried out in the liquid-handling robotic system.
A virtually indispensable method in molecular diagnostics is an amplification of a target—of the analyte—by a thermal cycling reaction, such as in a polymerase chain reaction (PCR) for example. Very small, only indirectly detectable amounts of analyte molecules are exponentially multiplied to detectable amounts.
A manipulation of samples which are to be amplified or which are amplified is extremely critical. Very small contaminations, via an aerosol formation for example, having, if present, even only single molecules would lead to sample material having false-positive or increased quantitative results. Therefore, it is customary in molecular diagnostics to carry out sample preparation and amplification in separate rooms. This is, however, very laborious and requires the handling of the samples by laboratory personnel.
An approach consists in a hermetic sealing of the titer plate with laminating film before carrying out the PCR, as described in DE 10 2005 059 535 A1. The titer plate must then no longer be opened in the same room. This measure of having separate rooms is contrary to the trend of integrating and automating analytical processes.
In order to analyze the resulting PCR product comprising the amplified analyte, optical methods based on real-time PCR are, for example, a possibility. There are, however, measurement methods in molecular diagnostics for electrical detection, with hybridization reactions being carried out in the methods. A method according to this type is known from WO 99/07879 A1. For this purpose, the resulting PCR product is transferred from the reaction vessel to a further vessel for the hybridization. A solution for a contamination-free transfer is in a hermetic integration of the vessels for the PCR and the hybridization in one closed cassette, such as, for example, in a quicklab® point-of-care cassette. This solution is, however, often too expensive for a routine, multifarious use and allows only comparatively low throughputs.
For an efficient detection, a product of the hybridization reaction with the amplified analyte can be electrically recorded. The quicklab® mentioned exemplarily is disclosed, for example, in DE 102 33 212 A1. A further arrangement for a biochip is known from DE 100 58 397 A1. DE 101 26 341 A1 teaches a biochip which, through hybridization with an analyte, changes an electrically recordable property.